The present invention relates generally to the field of radiation detection probes, and more specifically to a beta-sensitive radiation probe used to detect tissue labelled with beta-emitting radiopharmaceuticals.
The surgical excision of diseased tissue within the body, such as a tumor or abscess, is often complicated by the inability of the surgeon to visually differentiate the diseased tissue from the normal tissue. This problem is particularly acute in the field of surgical oncology, where small numbers of tumor cells can infiltrate areas of normal tissue both adjacent to and remote from the main tumor mass. Importantly, the failure to remove all of the diseased tissue during the procedure often results in a continuation or recurrence of the original problem.
One potential solution to this problem involves the detection of radiolabelled monoclonal antibodies and other radiopharmaceuticals, which are preferentially accumulated in diseased tissues such as cancer cells. Although intraoperative probes have been developed for use with several types of radioactive materials, the historical emphasis has been on the detection of gamma radiation in particular (gamma rays or photons). See Harris et al., Nucleonics 14:102-8 (1956); Morris et al., Phys. Med. Biol. 16:397-404 (1971); Woolfenden et al., Chest 85:84-88 (1984). Unfortunately, the prior art devices designed for use with gamma-emitting radiopharmaceuticals suffer from two significant problems: 1) the tumor-to-background ratios are non-optimal for the reliable differentiation of tumors, and 2) the detection of distant sources of gamma rays further reduces the already low tumor-to-background contrast. The longer path length of gamma radiation in body tissues creates significant background contamination from distant accumulations of the radiopharmaceutical, making the detection of nearby tagged tissues difficult or impossible.
As a result, there has been a renewed interest in developing intraoperative probes which focus primarily on the detection of beta emissions (positrons and/or electrons), particularly in light of the recent discovery of positron emitters with high affinity for cancers, such as 18F-labeled-Fluoro-2-Deoxy-D-Glucose (FDG). See Wahl et al., Cancer 67:1550-54 (1991). However, recent attempts to design an accurate beta-sensitive intraoperative probe have been complicated by the fact that positron-emitting radiopharmaceuticals such as 18F-FDG create two 511 keV annihilation photons when the positron subsequently collides with an electron. The detection of these highly penetrating gamma rays greatly reduces the observed tumor-to-background contrast gained by the use of these radiopharmaceuticals.
In response, several attempts have been made to design detectors to maximize the detected positron-to-photon ratio. One possible approach to limit the effect of the annihilation photon emissions relies upon energy discrimination to reduce the photon contribution to the signal. See Raylman et al., J. Nucl. Med. 36:1869-74 (1995). The dominant mode of interaction for the 511 keV photons produced during annihilation of the positron and electron is a Compton scattering of electrons, generally below 340 keV. In contrast, the positron interacts with the detector by producing a spectrum of energies, some of which are above the Compton edge of approximately 340 keV for annihilation photons. Accordingly, by selectively counting only those events with energies above the Compton edge, the probe becomes selectively sensitized to the electrons and positrons emitted by radiopharmaceuticals such as 18F, which create annihilation photons.
Unfortunately, most of the detectors proposed thus far for use as positron probes have utilized plastic scintillators. See Lerch et al., Am. J. Physiol. 242:H62-H67 (1982); Raylman et al., J. Nucl. Med. 35:909-13 (1994); Daghighian et al,, Med Phys. 36:1869-74 (1995). The application of the energy discrimination technique with plastic scintillators is problematic due to the poor energy resolution of this material, which is a measure of how well the energy of a specific type of radiation (such as gamma rays) can be defined. Moreover, inefficiencies in the collection of the scintillation light produced by the plastic scintillators also reduce the energy resolution of these detection devices.
An alternative method and device proposed and patented by Daghighian et al. involves the use of two separate plastic scintillation detectors, whereby the signals from the shielded outer detector are used to correct for photon contamination of the signal from the inner detector. See Daghighian et al., Med. Phys. 21:153-7 (1994); U.S. Pat. No. 5,008,546 to Mazziotta et al. Correction of signal contamination is accomplished by a weighted subtraction of the outer detector count rate from the inner detector count rate. The weighting factor is the ratio of the gamma counting efficiencies of the two detectors, which is calculated during a relatively simple calibration procedure.
While the use of a second detector to measure the background contamination is somewhat effective, this addition unfortunately results in a probe tip which is always physically larger than a single detector. Therefore, the practical application of this type of probe is problematic where space is a premium, such as with intraluminal probes and other situations where the surgical field is small. Moreover, the reduction of the surgical field continues to increase as minimally invasive surgical procedures are developed, and therefore a useful alternative to the two-detector method is needed. Furthermore, it is not clear that the background subtraction/weighting function remains constant when the probe is presented with gamma rays entering the detector volume other than through the front window. This problem is very often present in many common surgical applications.
Accordingly, there is still a substantial need in the art for an intraoperative probe which can differentiate diseased tissue based on beta emissions from a radiopharmaceutical. The probe must also have a minimal size for less intrusive operation during surgery, while at the same time provide increased sensitivity and selectivity.
The present invention contemplates a method for detecting radiopharmaceuticals within diseased tissue. In one embodiment, the method comprises the steps of a) providing: i) a patient having a region of diseased tissue, ii) a radiopharmaceutical capable of emitting beta particles and gamma radiation, and iii) an ion-implanted silicon detector; b) administering said radiopharmaceutical to said patient; and c) using said ion-implanted silicon detector to preferentially detect beta particles emitted from said radiopharmaceutical within said region over gamma radiation.
In one preferred embodiment, the step of discriminating a component of an electrical signal produced by said detector when struck by said beta particles and said gamma radiation. Said component of said electrical signal may be produced by said detector when struck by said gamma radiation.
While it is not intended that the present invention be limited by the particular radiopharmaceutical, a preferred pharmaceutical is 18F-labeled-Fluoro-2-Deoxy-D-Glucose.
The present invention also contemplates a probe system comprising a probe having an ion-implanted silicon detector, whereby beta particles emitted from a radiopharmaceutical within a diseased tissue are preferentially detected over gamma radiation. In one embodiment, the means for discriminating comprises stacked detectors.
In another preferred embodiment, said probe further comprises a means for discriminating a component of an electrical signal produced by said detector when struck by said beta particles and said gamma radiation, said means for discriminating coupled to said detector.
In another preferred embodiment, said component of said electrical signal is produced by said detector when struck by said gamma radiation.
In another preferred embodiment, said probe further comprises a) a preamplifier for amplifying said electrical signal, said preamplifier coupled to said detector; and b) an amplifier for further amplifying said electrical signal, said amplifier coupled between said preamplifier and said means for discriminating.
In another preferred embodiment, the probe system further comprises a counter for counting the number of received beta particles, said counter coupled to said means for discriminating.
In another preferred embodiment, the probe system further comprises a) a transmitter for transmitting said electrical signal as a transmitted signal, said transmitter coupled to said means for discriminating; and b) a receiver for receiving said transmitted signal, said receiver coupled to said counter.
In another embodiment, said probe further comprises a battery.
In another preferred embodiment, said transmitter is an optical transmitter, said receiver is an optical receiver and said transmitted signal is an optical signal. In an alternative embodiment, said optical transmitter is an infrared transmitter, said optical receiver is an infrared receiver and said optical signal is an infrared signal. In an alternative embodiment, said transmitter is a radio transmitter, said receiver is a radio receiver and said transmitted signal is a radio signal.
The present invention also contemplates a probe system for detecting radiation emitted from a radiopharmaceutical in a diseased tissue, comprising a) a probe having a radiation detector which generates an electrical signal in response to the passage of radiation into said detector from the radiopharmaceutical in the diseased tissue; and b) an optical transmitter coupled to said probe for transmitting said electrical signal as an optical signal to a remote location. Alternatively, the present invention contemplates a probe system for detecting radiation emitted from a radiopharmaceutical in a diseased tissue, comprising: a) a probe having a first radiation detector which generates an electrical signal in response to the passage of radiation into said first detector from a radiopharmaceutical in diseased tissue; and b) an optical transmitter coupled to said probe for transmitting said electrical signal as an optical signal to a remote location. In a preferred embodiment, the system further comprises a second radiation detector, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector.
The present invention also contemplates a probe comprising an ion-implanted silicon detector, whereby beta particles emitted from a radiopharmaceutical within a diseased tissue are preferentially detected over gamma radiation.
In another preferred embodiment, the probe further comprises a means for discriminating a component of an electrical signal produced by said detector when struck by said beta particles and said gamma radiation, said means for discriminating coupled to said detector.
In another preferred embodiment, said component of said electrical signal is produced by said detector when struck by said gamma radiation.
In another preferred embodiment, the probe further comprises a) a preamplifier for amplifying said electrical signal, said preamplifier coupled to said detector; and b) an amplifier for further amplifying said electrical signal, said amplifier coupled between said preamplifier and said means for discriminating.
In another preferred embodiment, the probe further comprises a counter for counting the number of received beta particles, said counter coupled between said amplifier and said means for discriminating.
The present invention is not limited by the number of detectors utilized. While the present invention contemplates any number of detectors, in another embodiment, the present invention contemplates a device comprising: a) a housing, comprising a rear portion and a front portion, said front portion comprising a tip; and b) first and second radiation detectors disposed within said housing at said tip, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector. While the present invention is not limited by the configuration of the detectors, in one embodiment, the first detector is positioned in front of the second detector in a manner such that gamma radiation reaching said tip of said device contacts said first detector prior to contacting said second detector.
Likewise, the present invention is not limited by the nature of the detectors. In one embodiment, the first and second detectors are semiconductor detectors. In a preferred embodiment, the semiconductor detectors are ion-implanted silicon detectors. In a particularly preferred embodiment, the semiconductor detectors are surface barrier detectors or positive intrinsic negative semiconductors. Moreover, while the present invention is not limited to the type of the detectors, in one embodiment the first and second detectors comprise circular silicon wafers of identical dimensions.
In another embodiment, the device further comprises first and second preamplifiers contained within said housing, said first preamplifier coupled to said first detector and said second preamplifier coupled to said second detector. While the present invention is not limited to a precise configuration, in one embodiment, the preamplifiers are both connected to a power supply.
In yet another embodiment, the device further comprises a radiation entrance window defining said tip and the end of the front portion of said housing. In a preferred embodiment, the radiation entrance window permits the transmission of gamma radiation and wherein the remainder of the housing blocks the transmission of gamma radiation. In such an embodiment, the radiation entrance window is preferably opaque and comprises aluminum.
The present invention also contemplates a device, comprising: a) an elongated housing, comprising a hand-graspable rear portion and a front portion, said front portion comprising a cylindrical tip; and b) first and second semiconductor radiation detectors disposed within said housing at said tip, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector.
In one embodiment, the device further comprises a radiation entrance window defining said tip and the end of the front portion of said housing. While the present invention is not limited to a specific configuration, in such an embodiment the first detector is positioned in front of said second detector relative to said radiation entrance window in a manner such that radiation reaching said tip of said device contacts said first detector prior to contacting said second detector.
The present invention also contemplates a device, comprising: a) an elongated housing, comprising a hand-graspable rear portion and a front portion, said front portion comprising a cylindrical tip having a radiation entrance window, wherein said radiation entrance window permits the transmission of gamma radiation and wherein the remainder of the housing blocks the transmission of gamma radiation; and b) first and second semiconductor radiation detectors disposed within said housing at said tip, wherein said first detector is positioned in front of said second detector relative to said radiation entrance window in a manner such that radiation reaching said tip of said device contacts said first detector prior to contacting said second detector, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector.
In another embodiment, the present invention contemplates a method for detecting radiopharmaceuticals within diseased tissue, comprising a) providing: 1) a patient having a region of diseased tissue, 2) a radiopharmaceutical capable of emitting beta particles, and 3) a device comprising a housing having a rear portion and a front portion, said front portion comprising a tip with first and second radiation detectors disposed within said housing at said tip, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector; b) administering said radiopharmaceutical to said patient; and c) detecting beta particles emitted from said radiopharmaceutical with said device within said region of said patient. The present invention is not limited by the nature of the device. However, in certain embodiments the device may have the characteristics described for the devices above.
In yet another embodiment, the present invention contemplates a method for detecting radiopharmaceuticals within diseased tissue, comprising: a) providing: 1) a patient having a region of diseased tissue, 2) a radiopharmaceutical capable of emitting beta particles and gamma radiation, and 3) a device comprising: i) an elongated housing, said housing comprising a hand-graspable rear portion and a front portion, said front portion comprising a cylindrical tip, and ii) first and second semiconductor detectors disposed within said housing at said tip, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector; b) administering said radiopharmaceutical to said patient; and c) detecting beta particles emitted from said radiopharmaceutical with said device within said region of said patient. The present invention is not limited by the nature of the device. However, in certain embodiments the device may have the characteristics described for the devices above.
In still another embodiment, the present invention contemplates a method for detecting radiopharmaceuticals within diseased tissue, comprising: a) providing: 1) a patient having a region of diseased tissue, 2) a radiopharmaceutical capable of emitting beta particles, and 3) a device comprising: i) an elongated housing, comprising a hand-graspable rear portion and a front portion, said front portion comprising a cylindrical tip having a radiation entrance window, wherein said radiation entrance window permits the transmission of gamma radiation and wherein the remainder of the housing blocks the transmission of gamma radiation, and ii) first and second semiconductor radiation detectors disposed within said housing at said tip, wherein said first detector is positioned in front of said second detector relative to said radiation entrance window in a manner such that radiation reaching said tip of said device contacts said first detector prior to contacting said second detector, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector; b) administering said radiopharmaceutical to said patient; and c) detecting beta particles emitted from said radiopharmaceutical with said device within said region of said patient. The present invention is not limited by the nature of the device. However, in certain embodiments the device may have the characteristics described for the devices above.
In another embodiment, the present invention contemplates a method for detecting radiopharmaceuticals within diseased tissue, comprising: a) providing: 1) a patient having a region of diseased tissue, 2) a radiopharmaceutical capable of emitting beta particles, and 3) a device comprising: i) a probe having a first radiation detector which generates an electrical signal in response to the passage of radiation into said first detector from a radiopharmaceutical in diseased tissue; and ii) an optical transmitter coupled to said probe for transmitting said electrical signal as an optical signal to a remote location; and b) administering said radiopharmaceutical to said patient; and c) detecting beta particles emitted from said radiopharmaceutical with said device within said region of said patient. In a preferred embodiment, the device further comprises a second radiation detector, said first detector capable of detecting beta particles and gamma radiation and serving to shield said second detector from at least a portion of the beta particles detected by said first detector.